Proteins modulation in human skeletal muscle in the early phase of adaptation to hypobaric hypoxia.
High altitude hypoxia is a paraphysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. In man, skeletal muscle, after prolonged exposure to hypoxia, undergoes mass reduction and alterations at the cellular level featuring a reduction of mitochondrial volume density, accumulation of lipofuscin, a product of lipid peroxidation, and dysregulation of enzymes whose time course is unknown. The effects of 7-9 days exposure to 4559 m (Margherita Hut, Monte Rosa, Italy) on the muscle proteins pattern were investigated, pre- and post-exposure, in ten young subjects, by 2-D DIGE and MS. Ten milligram biopsies were obtained from the mid part of the vastus lateralis muscle at sea level (control) and at altitude, after 7-9 days hypoxia. Differential analysis indicates that proteins involved in iron transport, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and oxidative stress responses were significantly (p<0.05) decreased in hypoxia. Parenthetically, hypoxia markers such as hypoxia inducible factor 1 alpha (HIF-1alpha) and pyruvate dehydrogenase kinase 1 (PDK1) were still at the pre-hypoxia levels, whereas the mammalian target of rapamycin (mTOR), a marker of protein synthesis, was reduced.
Viganò
Agnese
A
Department of Sciences and Biomedical Technologies, University of Milan, LITA, Milan, Italy.
Ripamonti
Marilena
M
De Palma
Sara
S
Capitanio
Daniele
D
Vasso
Michele
M
Wait
Robin
R
Lundby
Carsten
C
Cerretelli
Paolo
P
Gelfi
Cecilia
C
D000222:Adaptation, Physiological; D000328:Adult; D001274:Atmospheric Pressure; D001707:Biopsy, Needle; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D003285:Contractile Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D058570:TOR Serine-Threonine Kinases; D020298:U937 Cells
D002352:Carrier Proteins; D003285:Contractile Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009124:Muscle Proteins; C000631429:PDK1 protein, human; D011506:Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011494:Protein Kinases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases